title: C/EBPβ regulates dexamethasone-induced muscle cell atrophy and expression of atrogin-1 and MuRF1.
abstract: Muscle wasting in catabolic patients is in part mediated by glucocorticoids and is associated with increased expression and activity of the transcription factor C/EBPβ. It is not known, however, if C/EBPβ is causally linked to glucocorticoid-induced muscle atrophy. We used dexamethasone-treated L6 myoblasts and myotubes to test the role of C/EBPβ in glucocorticoid-induced expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF1, protein degradation, and muscle atrophy by transfecting cells with C/EBPβ siRNA. In myoblasts, silencing C/EBPβ expression with siRNA inhibited dexamethasone-induced increase in protein degradation, atrogin-1 and MuRF1 expression, and muscle cell atrophy. Similar effects of C/EBPβ siRNA were seen in myotubes except that the dexamethasone-induced increase in MuRF1 expression was not affected by C/EBPβ siRNA in myotubes. In additional experiments, overexpressing C/EBPβ did not influence atrogin-1 or MuRF1 expression in myoblasts or myotubes. Taken together, our observations suggest that glucocorticoid-induced muscle wasting is at least in part regulated by C/EBPβ. Increased C/EBPβ expression alone, however, is not sufficient to upregulate atrogin-1 and MuRF1 expression.
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Surgery, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gonnella
authors.forename: Nima
authors.initials: N
authors.lastname: Alamdari
authors.forename: Steven
authors.initials: S
authors.lastname: Tizio
authors.forename: Zaira
authors.initials: Z
authors.lastname: Aversa
authors.forename: Victoria
authors.initials: V
authors.lastname: Petkova
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D000818:Animals; D001284:Atrophy; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D005938:Glucocorticoids; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D003907:Dexamethasone; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases